The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

Abstract Inflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a consid...

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Autores principales:	Rayko Evstatiev, Adam Cervenka, Tina Austerlitz, Gunther Deim, Maximilian Baumgartner, Andrea Beer, Anita Krnjic, Christina Gmainer, Michaela Lang, Adrian Frick, Helga Schachner, Vineeta Khare, Christoph Gasche
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c870e4f379f74efaa91213d474882b21
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spelling	oai:doaj.org-article:c870e4f379f74efaa91213d474882b212021-12-02T11:35:41ZThe food additive EDTA aggravates colitis and colon carcinogenesis in mouse models10.1038/s41598-021-84571-52045-2322https://doaj.org/article/c870e4f379f74efaa91213d474882b212021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84571-5https://doaj.org/toc/2045-2322Abstract Inflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.Rayko EvstatievAdam CervenkaTina AusterlitzGunther DeimMaximilian BaumgartnerAndrea BeerAnita KrnjicChristina GmainerMichaela LangAdrian FrickHelga SchachnerVineeta KhareChristoph GascheNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rayko Evstatiev Adam Cervenka Tina Austerlitz Gunther Deim Maximilian Baumgartner Andrea Beer Anita Krnjic Christina Gmainer Michaela Lang Adrian Frick Helga Schachner Vineeta Khare Christoph Gasche The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models
description	Abstract Inflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.
format	article
author	Rayko Evstatiev Adam Cervenka Tina Austerlitz Gunther Deim Maximilian Baumgartner Andrea Beer Anita Krnjic Christina Gmainer Michaela Lang Adrian Frick Helga Schachner Vineeta Khare Christoph Gasche
author_facet	Rayko Evstatiev Adam Cervenka Tina Austerlitz Gunther Deim Maximilian Baumgartner Andrea Beer Anita Krnjic Christina Gmainer Michaela Lang Adrian Frick Helga Schachner Vineeta Khare Christoph Gasche
author_sort	Rayko Evstatiev
title	The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models
title_short	The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models
title_full	The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models
title_fullStr	The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models
title_full_unstemmed	The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models
title_sort	food additive edta aggravates colitis and colon carcinogenesis in mouse models
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c870e4f379f74efaa91213d474882b21
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The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

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